Ukraine has one of the highest opioid use prevalence levels in Eastern Europe and worldwide, causing substantial morbidity and mortality through co-occurring epidemics involving infectious diseases, in particular HIV, which is primarily driven by injecting drug use. The current response to the problem of HIV and opioid use disorders in Ukraine is insufficient. Novel approaches are needed to address coverage gaps and optimize patient outcomes. Opioid agonist therapy (OAT) was demonstrated to be an effective and cost-effective intervention in reducing harm associated with opioid use. Ukraine has implemented methadone therapy since 2008; however, only 2.7% of the 310,000 Ukrainian PWIDs are receiving OAT, which is far too low to reduce drug injection-mediated HIV transmission. Expanding OAT availability to primary healthcare (PHC) settings may reduce barriers to entry and increase retention in treatment programs. An alternative to OAT, an injectable opioid receptor antagonist, extended-release naltrexone (XR-NTX) is another evidence-based treatment for opioid dependence. By reducing drug craving and illicit drug use, XR-NTX reduces HIV risk behavior and improves quality of life compared to placebo. XR-NXT offers a promising alternative pharmacological treatment for opioid use disorders that would likely target a different sub-population of drug users ? specifically those who cannot or is unwilling to receive agonist-based therapy. The main advantage of XR-NTX in comparison with oral naltrexone is that it is administered as a monthly injection rather than taken daily. This was shown to improve treatment compliance; however, adherence is still problematic. The hypothesis of this research project is that the novel interventions: a) expanding OST delivery to PHC facilities; and b) treating opioid dependence with XR-NTX in Ukraine are cost effective relative to the current standard of care in Ukraine. Outcomes of these interventions will be evaluated at both patient and population levels. The study will employ a mathematical modeling approach: a state transition Markov model will be developed to assess patient-level outcomes; and a dynamic compartmental HIV transmission model will estimate the benefits from the interventions at the population level. The analysis will capitalize on the available literature and two recent studies in which I have been involved: 1) Formative Research: Piloting the Provision of Integrated Care to Opioid Drug Users in Primary Healthcare Facilities in Ukraine (study period: 2014-2015); and 2) Expanding Medication-Assisted Therapies in Ukraine (R01 DA033679, study period: 2012-2017). The results of the proposed study can potentially lead to policy changes in treatment of opioid dependence in Eastern Europe and Central Asia, inform priorities for future comparative effectiveness research, and motivate similar policy research in other countries with high burden of opioid drug use and HIV.